In this renewal proposal we set forth our plans to complete the stereospecific total synthesis of maytansine, a potent tumor-inhibitor. Work so far has achieved three of seven specific aims originally outlined in the parent proposal. Current specific aims include the stereocontrolled construction of both C10-C18 and C1-C9 fragments, synthesis of natural and analog C3 ester sidechains, and plans to control C10 stereochemistry. Once these goals have been achieved, our newly-developed methodology should enable the total synthesis of all known pharmacologically active maytansinoids, including many readily accessible carbinolamide-containing model compounds. Additionally, we will apply our new methodology for lactam formation not only to maytansinoids, but also to the synthesis of tumor-inhibitory spermidine alkaloids, cyclic polypeptides of biological interest, and to other functional groups such as thioesters. Lastly, our long-range plans for the total synthesis of more complex, anti-tumor ansamycins, specifically the family of rifamycins, are presented. Throughout this project, the importance of versatility and flexibility is stressed, especially with regard to the preparation of structural analogs for clinical testing.